Our investigations are designed to characterize the role the immune system plays in the host's interaction with antigens in the intestinal tract. Antigen in the intestine can interact with antigen-sensitive cells in the intestine as well as alter the reactivity of antigen-sensitive cells in extraintestinal sites. During the proposed project period, we plan first to characterize the interactions between certain classes of antigens (protein, carbohydrate, erythrocyte, reactive chemical and cellular) administered by the intestinal route and antigen-sensitive cells in Peyer's patches. Second, we plan to characterize the ability of antigens administered by the intestinal route to alter the reactivity of antigen-sensitive cells in extraintestinal sites including the spleen, mesenteric lymph nodes, peripheral lymph nodes, and thoracic duct lymph. B cells will be examined for induction to humoral antibody synthesis. T cells will be examined for induction of helper function, suppressor function, cytotoxic T cells and T cells mediating delayed-type hypersensitivity responses. Finally, applying basic concepts of cellular immunology, we will initiate investigations which will attempt to characterize the role specific immune effector mechanisms play in the pathogenesis of immune tissue injury in gluten-sensitive enteropathy and ulcerative colitis. Defining the mechanisms by which antigens in the intestine influence the reactivity of antigen-sensitive cells in intestinal and extraintestinal sites should lead to greater understanding of the role the immune system plays in the host's interaction with viable and non-viable antigens and in the pathogenesis of immune tissue injury in certain intestinal diseases.